1. Field of the Invention
The present invention relates to the use of N,N'-dibenzylethylenediamine-N,N'-diacetic acid derivatives in a composition for topical application, as depigmenting and/or bleaching agents for human skin.
2. Description of the Background
The color of the skin depends on different factors and, in particular, the seasons of the year, race and sex, and it is mainly determined by the concentration of melanin produced by the melanocytes. In addition, at different periods in their lives, certain individuals develop dark and/or colored blemishes on the skin and more especially on the hands, making the skin non-uniform. These blemishes are also due to a large concentration of melanin in the keratinocytes at the skin surface.
For several years, attempts have been made to decrease and/or slow down the production of the melanin in order to depigment or bleach the skin, by acting on one or more of the points of the intracellular biochemical synthesis of melanin. In this regard, for many years, various molecules have been used and tested as depigmenting or bleaching agents.
The mechanism for the formation of skin pigmentation, that to say the formation of melanin, is particularly complex and schematically involves the following main steps:
Tyrosine.fwdarw.Dopa.fwdarw.Dopaquinone.fwdarw.Dopachrome.fwdarw.Melanin
Tyrosinase is the essential enzyme involved in this reaction sequence. It especially catalyses the reaction in which tyrosine is converted into dopa (dihydroxyphenylalanine) and the reaction in which dopa is converted into dopaquinone. Tyrosinase acts only when it is in the mature state, under the action of certain biological factors.
A substance is recognized as being depigmenting if it acts directly on the viability of the epidermal melanocytes in which melanogenesis takes place and/or if it interferes with one of the steps in the biosynthesis of melanin either by inhibiting one of the enzymes involved in melanogenesis or by becoming intercalated as a structural analogue of one of the chemical compounds in the melanin synthesis chain, whereby this chain may be blocked and ensure the depigmentation.
The substances most commonly used as depigmenting agents in compositions are, in particular, compounds such as vitamin C, vitamin C derivatives or vitamin E derivatives, arbutin, hydroquinone, kojic acid, placental derivatives and glutathione and its derivatives. These various compounds are known to act on the synthesis and/or activity of tyrosinase, the enzyme involved in the synthesis of melanin, or to reduce the amount of melanin formed or alternatively to stimulate the removal of melanin via the keratinocytes. Unfortunately, they are either toxic, as in the case of hydroquinone, or unstable in solution, as in the case of vitamin C and kojic acid, which complicates the manufacture of the composition somewhat, or else they may emit unpleasant odors and in particular sulfur odors in the case of glutathione, which consequently limits their use. Furthermore, these compounds are very limited in number.
Thus, there continues to be a need for a skin-bleaching agent which is as effective as the known agents, but which does not have their disadvantages, that is to say that it is stable in a composition, is non-toxic to the skin and has no unpleasant odor and especially insofar as this agent is applied to the skin.
In this regard copper-chelating agents have been used for a long time as depigmenting agents. Indeed, these chelating agents act on the copper ions present at the active site of tyrosinase, the key enzyme in melanogenesis. For example, it has been reported that L-mimosine, which is a natural hydroxypyridinone which forms very stable complexes with copper, is a good inhibitor of tyrosinase (Hider et al, Biochem. J. 1989, 257:289), as is kojic acid which also interacts strongly with copper. However, these chelating agents have the drawback of being toxic, especially L-mimosine, and of having side-effects associated with interference with the metabolism of certain metals.
On the other hand, much less work has been carried out with iron-chelating agents as depigmenting agents. Certain chelating agents are described as being capable of depigmenting mink skin (Blumenkrantz et al, Acta Agric. Scand. 1987, 37:375). However, the compounds described in this publication are toxic to a certain extent, which does not permit their topical use on human skin.
Moreover, lactoferrin hydrolysates have been patented as depigmenting agents (Morinaga, JP-A-04059714 and EP-A-438,750). However, the use of products of animal origin is to be avoided.
It is noted, however, that compounds, which are known as iron-chelating agents and which are commonly used in the cosmetic or dermatological field, have never been used to date to depigment or bleach the skin.